Group A streptococcal infection

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Group A streptococcal infection
Streptococcus pyogenes.jpg
Streptococcus pyogenes
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Group A streptococcal infections are a number of infections with Streptococcus pyogenes , a group A streptococcus (GAS). [1] S. pyogenes is a species of beta-hemolytic Gram-positive bacteria that is responsible for a wide range of infections that are mostly common and fairly mild. If the bacteria enter the bloodstream an infection can become severe and life-threatening, and is called an invasive GAS (iGAS). [2] [3]

Contents

Infection of GAS may spread through direct contact with mucus or sores on the skin. [2] GAS infections can cause over 500,000 deaths per year. [4] Despite the emergence of antibiotics as a treatment for group A streptococcus, cases of iGAS are an increasing problem, particularly on the continent of Africa. [5]

There are many other species of Streptococcus , including group B streptococcus Streptococcus agalactiae , and Streptococcus pneumoniae , which cause other types of infections. Several virulence factors contribute to the pathogenesis of GAS, such as M protein, hemolysins, and extracellular enzymes.

Types of infection

Group A β-hemolytic streptococcus can cause infections of the throat and skin. [6] These may vary from very mild conditions to severe, life-threatening diseases. Although it is not completely clear what causes different people to develop different diseases as a result of infection with the same pathogenic bacteria, it is suspected that host phenotypic and epigenetic factors are the source of such variation. Indeed, the many virulence factors of GAS can influence the epigenetics of the host. Furthermore, persons with suppressed or compromised immune systems may be more susceptible to certain diseases caused by GAS than other persons with intact immune systems. A 2019 study shows that GAS's evasion of immune detection is facilitated by protein S, an extracellular and cell wall-associated protein that enables it to camouflage itself by binding fragments of lysed red blood cells. [7]

Humans may also carry the GAS either on the skin or in the throat and show no symptoms. [8] These carriers are less contagious than symptomatic carriers of the bacteria. [8]

The non-invasive infections caused by GAS tend to be less severe and more common. They occur when the bacteria colonizes the throat area, where it recognizes epithelial cells. [9] The two most prominent infections of GAS are both non-invasive: strep throat (pharyngitis) where it causes 15–30% of the childhood cases and 10% of adult cases, and impetigo. [4] These may be effectively treated with antibiotics. Scarlet fever is also a non-invasive infection caused by GAS, although much less common.

The invasive infections caused by Group A β-hemolytic streptococcus tend to be more severe and less common. These occurs when the bacterium is able to infect areas where bacteria are not usually found, such as blood and organs. [8] The diseases that may be caused as a result of this include streptococcal toxic shock syndrome (STSS), necrotizing fasciitis (NF), pneumonia, and bacteremia. [4]

In addition, infection of GAS may lead to further complications and health conditions, namely acute rheumatic fever and poststreptococcal glomerulonephritis.

Most common:

Less common:

(*Note that meningitis, sinusitis and pneumonia can all be caused by Group A Strep, but are much more commonly associated with Streptococcus pneumoniae and should not be confused.)

Severe infections

Some strains of group A streptococci (GAS) cause severe infection. Severe infections are usually invasive, meaning that the bacteria has entered parts of the body where bacteria are not usually found, such as the blood, lungs, deep muscle or fat tissue. [10] Those at greatest risk include children with chickenpox; persons with suppressed immune systems; burn victims; elderly persons with cellulitis, diabetes, vascular disease, or cancer; and persons taking steroid treatments or chemotherapy. Intravenous drug users and homeless also are at high risk. [11] GAS is an important cause of puerperal fever worldwide, causing serious infection and, if not promptly diagnosed and treated, death in newly delivered mothers. Severe GAS disease may also occur in healthy persons with no known risk factors.

All severe GAS infections may lead to shock, multisystem organ failure, and death. Early recognition and treatment are critical. [12] [13] Diagnostic tests include blood counts and urinalysis as well as cultures of blood or fluid from a wound site.

Severe Group A streptococcal infections often occur sporadically but can be spread by person-to-person contact. [14] Close contacts of people affected by severe Group A streptococcal infections, defined as those having had prolonged household contact in the week before the onset of illness, may be at increased risk of infection. This increased risk may be due to a combination of shared genetic susceptibility within the family, close contact with carriers, and the virulence of the Group A streptococcal strain that is involved. [15]

Public health policies internationally reflect differing views of how the close contacts of people affected by severe Group A streptococcal infections should be treated. Health Canada [16] and the US CDC recommend close contacts see their doctor for full evaluation and may require antibiotics; [17] current UK Health Protection Agency guidance is that, for a number of reasons, close contacts should not receive antibiotics unless they are symptomatic but that they should receive information and advice to seek immediate medical attention if they develop symptoms. [15] However, guidance is clearer in the case of mother-baby pairs: both mother and baby should be treated if either develops an invasive GAS infection within the first 28 days following birth [15] (though some evidence suggests that this guidance is not routinely followed in the UK [18] ).

Diagnosis

Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Main Streptococcus groups are included as "Strep." at bottom left. Diagnostic algorithm of possible bacterial infection.png
Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Main Streptococcus groups are included as "Strep." at bottom left.

Diagnosis is by a swab of the affected area for laboratory testing. A Gram stain is performed to show Gram-positive cocci in chains. Then, the organism is cultured on blood agar. The rapid pyrrolidonyl arylamidase (PYR) test is commonly used, wherein a positive reaction confers a presumptive identification of group A beta-hemolytic streptococci if the appearance and clinical context is consistent. GBS gives a negative finding on the PYR test test. [19] There are also latex agglutination kits which can distinguish each of the main groups seen in clinical practice.

Prevention

S. pyogenes infections are best prevented through effective hand hygiene. [20] No vaccines are currently available to protect against S. pyogenes infection, although research has been conducted into the development of one. [21] Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and number of people that will be needed for appropriate trials for safety and efficacy of the vaccine. [21] [22]

Treatment

The treatment of choice is penicillin, and the duration of treatment is around 10 days. [23] Antibiotic therapy (using injected penicillin) has been shown to reduce the risk of acute rheumatic fever. [24] In individuals with a penicillin allergy, erythromycin, other macrolides, and cephalosporins have been shown to be effective treatments. [25]

Treatment with ampicillin/sulbactam, amoxicillin/clavulanic acid, or clindamycin is appropriate if deep oropharyngeal abscesses are present, in conjunction with aspiration or drainage. [26] In cases of streptococcal toxic shock syndrome, treatment consists of penicillin and clindamycin, given with intravenous immunoglobulin. [27]

For toxic shock syndrome and necrotizing fasciitis, high-dose penicillin and clindamycin are used. Additionally, for necrotizing fasciitis, surgery is often needed to remove damaged tissue and stop the spread of the infection. [20]

No instance of penicillin resistance has been reported to date, although since 1985, many reports of penicillin tolerance have been made. [28] The reason for the failure of penicillin to treat S. pyogenes is most commonly patient noncompliance, but in cases where patients have been compliant with their antibiotic regimen, and treatment failure still occurs, another course of antibiotic treatment with cephalosporins is common. [25]

The 30-valent N-terminal M-protein-based vaccine as well as the M-protein vaccine (minimal epitope J8 vaccine) are two vaccines for GAS that are currently getting close or becoming clinical studies, however, other vaccines using conserved epitopes are progressing. [29]

Epidemiology

Cases of GAS are still present today, but were also evident before World War I. This was shown by a training camp located in Texas, where a harmful strain of pneumonia complicating measles was caused by a strain of Streptococcus. [30] Existence of streptococci strains was additionally found in World War II. An epidemic of streptococcal infection in the United States Navy during this war indicated that this type of disease was able to exist and spread in formerly unexposed individuals by environments that serological types of group A streptococci preferred. [30] In later years, a positive test result for the presence of group A streptococci was found in 32.1 percent of individuals after throat cultures were carried out in a 20 yearlong (1953/1954-1973/1974) study performed in Nashville, TN. [30] Also, from 1972 to 1974, recurring GAS illness was observed with a prevalence of 19 percent in school-aged children as well as a prevalence rate of 25 percent in families. [30] The severity of streptococcal infections has decreased over the years, and so has rheumatic fever (a sequelae of GAS) which is indicated by the change in numerous hospitals from containing wards allocated for the sole purpose of treating rheumatic fever to hardly seeing the disease at all. [30] Environmental factors, such as less crowding and the increase of family living space, can account for the reduction in incidence and severity of group A streptococci. [30] With more space for individuals to reside in, it provides the bacteria with less opportunities to spread from person to person. This is especially important considering an estimated 500,000 deaths worldwide all occurring after acute rheumatic fever, invasive infection, or subsequent heart disease can be accredited to GAS. [31] This number is quite large, often leaving the health care system encumbered, since 91 percent of patients infected with invasive GAS need to be hospitalized with 8950–11,500 episodes and 1050-1850 deaths taking place each year. [31] A later study that occurred from 2005 to 2012 found that there were 10,649-13,434 cases consequently resulting in 1136-1607 deaths per year. [29]

Complications

Acute rheumatic fever

Acute rheumatic fever (ARF) is a complication of respiratory infections caused by GAS. The M-protein generates antibodies that cross-react with autoantigens on interstitial connective tissue, in particular of the endocardium and synovium, that can lead to significant clinical illness.

Although common in developing countries, ARF is rare in the United States, possibly secondary to improved antibiotic treatment, with small isolated outbreaks reported only occasionally. It is most common among children between 5 and 15 years old and occurs 1–3 weeks after an untreated GAS pharyngitis, but caution is advised when interpreting the demographics of the contemporary picture of pediatric cases in the United States. [32]

ARF is often clinically diagnosed based on Jones Criteria, which include: pancarditis, migratory polyarthritis of large joints, subcutaneous nodules, erythema marginatum, and sydenham chorea (involuntary, purposeless movement). The most common clinical finding is a migratory arthritis involving multiple joints. [33]

Other indicators of GAS infection such as a DNAase or ASO serology test must confirm the GAS infection. Other minor Jones Criteria are fever, elevated ESR and arthralgia. One of the most serious complications is pancarditis, or inflammation of all three heart tissues. A fibrinous pericarditis can develop with a classic friction rub that can be auscultated. This will give increasing pain upon reclining.

Further endocarditis can develop with aseptic vegetations along the valve closure lines, in particular the mitral valve. Chronic rheumatic heart disease mostly affects the mitral valve, which can become thickened with calcification of the leaflets, often causing fusion of the commissures and chordae tendineae.

Other findings of ARF include erythema marginatum (usually over the spine or other bony areas) and a red expanding rash on the trunk and extremities that recurs over weeks to months. Because of the different ways ARF presents itself, the disease may be difficult to diagnose.

A neurological disorder, Sydenham chorea, can occur months after an initial attack, causing jerky involuntary movements, muscle weakness, slurred speech, and personality changes. Initial episodes of ARF, as well as recurrences, can be prevented by treatment with appropriate antibiotics.

It is important to distinguish ARF from rheumatic heart disease. ARF is an acute inflammatory reaction with pathognomonic Aschoff bodies histologically and RHD is a non-inflammatory sequela of ARF.

Post-streptococcal glomerulonephritis

Post-streptococcal glomerulonephritis (PSGN) is an uncommon complication of either a strep throat or a streptococcal skin infection. It is classified as a type III hypersensitivity reaction. Symptoms of PSGN develop within 10 days following a strep throat or 3 weeks following a GAS skin infection. PSGN involves inflammation of the kidney. Symptoms include pale skin, lethargy, loss of appetite, headache, and dull back pain. Clinical findings may include dark-colored urine, swelling of different parts of the body (edema), and high blood pressure. Treatment of PSGN consists of supportive care.

PANDAS

Obsessive–compulsive disorder and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. [34] [35] [36] Its potential effect was described in 1998 by the controversial hypothesis called PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), a condition thought to be triggered by GABHS infections. [37] [38] The PANDAS hypothesis is unconfirmed and unsupported by data, and two new categories have been proposed: PANS (pediatric acute-onset neuropsychiatric syndrome) and CANS (childhood acute neuropsychiatric syndrome). [35] [36] The CANS/PANS hypotheses include different possible mechanisms underlying acute-onset neuropsychiatric conditions, but do not exclude GABHS infections as a cause in a subset of individuals. [35] [36] PANDAS, PANS and CANS are the focus of clinical and laboratory research but remain unproven. [34] [35] [36]

Related Research Articles

<i>Streptococcus</i> Genus of bacteria

Streptococcus is a genus of gram-positive coccus or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales, in the phylum Bacillota. Cell division in streptococci occurs along a single axis, so as they grow, they tend to form pairs or chains that may appear bent or twisted. This differs from staphylococci, which divide along multiple axes, thereby generating irregular, grape-like clusters of cells. Most streptococci are oxidase-negative and catalase-negative, and many are facultative anaerobes.

<i>Streptococcus pyogenes</i> Species of bacterium

Streptococcus pyogenes is a species of Gram-positive, aerotolerant bacteria in the genus Streptococcus. These bacteria are extracellular, and made up of non-motile and non-sporing cocci that tend to link in chains. They are clinically important for humans, as they are an infrequent, but usually pathogenic, part of the skin microbiota that can cause Group A streptococcal infection. S. pyogenes is the predominant species harboring the Lancefield group A antigen, and is often called group A Streptococcus (GAS). However, both Streptococcus dysgalactiae and the Streptococcus anginosus group can possess group A antigen as well. Group A streptococci, when grown on blood agar, typically produce small (2–3 mm) zones of beta-hemolysis, a complete destruction of red blood cells. The name group A (beta-hemolytic) Streptococcus is thus also used.

<span class="mw-page-title-main">Scarlet fever</span> Infectious disease caused by Streptococcus pyogenes

Scarlet fever, also known as scarlatina, is an infectious disease caused by Streptococcus pyogenes, a Group A streptococcus (GAS). It most commonly affects children between five and 15 years of age. The signs and symptoms include a sore throat, fever, headache, swollen lymph nodes, and a characteristic rash. The face is flushed and the rash is red and blanching. It typically feels like sandpaper and the tongue may be red and bumpy. The rash occurs as a result of capillary damage by exotoxins produced by S.pyogenes. On darker-pigmented skin the rash may be hard to discern.

<span class="mw-page-title-main">Streptococcal pharyngitis</span> Medical condition

Streptococcal pharyngitis, also known as streptococcal sore throat, is pharyngitis caused by Streptococcus pyogenes, a gram-positive, group A streptococcus. Common symptoms include fever, sore throat, red tonsils, and enlarged lymph nodes in the front of the neck. A headache and nausea or vomiting may also occur. Some develop a sandpaper-like rash which is known as scarlet fever. Symptoms typically begin one to three days after exposure and last seven to ten days.

<span class="mw-page-title-main">Pharyngitis</span> Inflammation of the back of the throat

Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse voice. Symptoms usually last 3–5 days, but can be longer depending on cause. Complications can include sinusitis and acute otitis media. Pharyngitis is a type of upper respiratory tract infection.

<span class="mw-page-title-main">Sore throat</span> Medical condition

Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include:

<span class="mw-page-title-main">Rheumatic fever</span> Post-streptococcal inflammatory disease

Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful joints, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of the cases. Damage to the heart valves, known as rheumatic heart disease (RHD), usually occurs after repeated attacks but can sometimes occur after one. The damaged valves may result in heart failure, atrial fibrillation and infection of the valves.

<span class="mw-page-title-main">Tonsillitis</span> Inflammation of the tonsils

Tonsillitis is inflammation of the tonsils in the upper part of the throat. It can be acute or chronic. Acute tonsillitis typically has a rapid onset. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and enlarged lymph nodes around the neck. Complications include peritonsillar abscess (Quinsy).

<span class="mw-page-title-main">Erythema marginatum</span> Medical condition

Erythema marginatum is an acquired skin condition which primarily affects the arms, trunk, and legs. It is a type of erythema characterised by bright pink or red circular lesions which have sharply-defined borders and faint central clearing. The lesions typically range from 3 to 10 cm in size, and are distributed symmetrically over the torso and inner surfaces of the limbs and extensor surfaces. The lesions last between one and four weeks but have been known to be present on patients for as long as several months.

A complication in medicine, or medical complication, is an unfavorable result of a disease, health condition, or treatment. Complications may adversely affect the prognosis, or outcome, of a disease. Complications generally involve a worsening in the severity of the disease or the development of new signs, symptoms, or pathological changes that may become widespread throughout the body and affect other organ systems. Thus, complications may lead to the development of new diseases resulting from previously existing diseases. Complications may also arise as a result of various treatments.

<i>Streptococcus agalactiae</i> Species of bacterium

Streptococcus agalactiae is a gram-positive coccus with a tendency to form chains. It is a beta-hemolytic, catalase-negative, and facultative anaerobe.

<span class="mw-page-title-main">Group B streptococcal infection</span> Medical condition

Group B streptococcal infection, also known as Group B streptococcal disease or just Group B strep infection, is the infectious disease caused by the bacterium Streptococcus agalactiae, which is the most common human pathogen belonging to the group B of the Lancefield classification of streptococci—hence the group B stretococcal (GBS) infection nomenclature. Infection with GBS can cause serious illness and sometimes death, especially in newborns, the elderly, and people with compromised immune systems. The most severe form of group B streptococcal disease is neonatal meningitis in infants, which is frequently lethal and can cause permanent neuro-cognitive impairment.

Anti-streptolysin O is the antibody made against streptolysin O, an immunogenic, oxygen-labile streptococcal hemolytic exotoxin produced by most strains of group A and many strains of groups C and G Streptococcus bacteria. The "O" in the name stands for oxygen-labile; the other related toxin being oxygen-stable streptolysin-S. The main function of streptolysin O is to cause hemolysis —in particular, beta-hemolysis.

<span class="mw-page-title-main">Rapid strep test</span> Test for strep throat

The rapid strep test (RST) is a rapid antigen detection test (RADT) that is widely used in clinics to assist in the diagnosis of bacterial pharyngitis caused by group A streptococci (GAS), sometimes termed strep throat. There are currently several types of rapid strep test in use, each employing a distinct technology. However, they all work by detecting the presence of GAS in the throat of a person by responding to GAS-specific antigens on a throat swab.

<i>Streptococcus dysgalactiae</i> Species of bacterium

Streptococcus dysgalactiae is a gram positive, beta-haemolytic, coccal bacterium belonging to the family Streptococcaceae. It is capable of infecting both humans and animals, but is most frequently encountered as a commensal of the alimentary tract, genital tract, or less commonly, as a part of the skin flora. The clinical manifestations in human disease range from superficial skin-infections and tonsillitis, to severe necrotising fasciitis and bacteraemia. The incidence of invasive disease has been reported to be rising. Several different animal species are susceptible to infection by S. dysgalactiae, but bovine mastitis and infectious arthritis in lambs have been most frequently reported.

<span class="mw-page-title-main">Streptococcal intertrigo</span> Medical condition

Streptococcal intertrigo is a skin condition that is secondary to a streptococcal bacterial infection. It is often seen in infants and young children and can be characterized by a fiery-red color of the skin, foul odor with an absence of satellite lesions, and skin softening in the neck, armpits or folds of the groin. Newborn children and infants commonly develop intertrigo because of physical features such as deep skin folds, short neck, and flexed posture. Prompt diagnosis by a medical professional and treatment with topical and/or oral antibiotics can effectively relieve symptoms.

Perianal cellulitis, also known as perianitis or perianal streptococcal dermatitis, is a bacterial infection affecting the lower layers of the skin (cellulitis) around the anus. It presents as bright redness in the skin and can be accompanied by pain, difficulty defecating, itching, and bleeding. This disease is considered a complicated skin and soft tissue infection (cSSTI) because of the involvement of the deeper soft tissues.

Bacteriophage T12 is a bacteriophage that infects Streptococcus pyogenes bacteria. It is a proposed species of the family Siphoviridae in the order Caudovirales also known as tailed viruses. It converts a harmless strain of bacteria into a virulent strain. It carries the speA gene which codes for erythrogenic toxin A. speA is also known as streptococcal pyogenic exotoxin A, scarlet fever toxin A, or even scarlatinal toxin. Note that the name of the gene "speA" is italicized; the name of the toxin "speA" is not italicized. Erythrogenic toxin A converts a harmless, non-virulent strain of Streptococcus pyogenes to a virulent strain through lysogeny, a life cycle which is characterized by the ability of the genome to become a part of the host cell and be stably maintained there for generations. Phages with a lysogenic life cycle are also called temperate phages. Bacteriophage T12, proposed member of family Siphoviridae including related speA-carrying bacteriophages, is also a prototypic phage for all the speA-carrying phages of Streptococcus pyogenes, meaning that its genome is the prototype for the genomes of all such phages of S. pyogenes. It is the main suspect as the cause of scarlet fever, an infectious disease that affects small children.

<span class="mw-page-title-main">2022–2023 United Kingdom group A streptococcus outbreak</span> Ongoing disease outbreak in the UK

In late 2022, an ongoing disease outbreak caused by the bacterium Streptococcus pyogenes, a Lancefield group A streptococcus, began in the United Kingdom. It is often referred to as the Strep A outbreak in the media. These bacteria cause group A streptococcal infections and scarlet fever. In the UK, 516 deaths from iGAS have been recorded, of which 61 were children, 52 in England, five in Wales, three in Scotland, and one in Northern Ireland.

Streptococcosis are diseases varying from mild to fatal side effects of the infection which originate from the bacterial group streptococcus. Some of the areas of infection include wounds, body tissue, and respiratory areas. Research within horses, dogs, cats, wound injuries and swine infections have been done to document specific side effects from streptococcosis. Streptococcosis can occur to both humans and animals, the most common including horses, guinea pigs, dogs, cats and fish; while uncommon animals infected include monkeys, cattle, sheep, goats, ferrets and poultry. The wide range of diseases is due to the variability of streptococcus strains which thus creates multiple species for the diseases to occur.

References

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Note: Elements of the original text of this article are taken from the NIH Fact Sheet "Group A Streptococcal Infections", dated March 1999. As a work of the U.S. Federal Government without any other copyright notice, this is assumed to be a public domain resource.

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